Obesity, Inflammation and BPH

肥胖、炎症和良性前列腺增生

• 批准号: 8566167
• 负责人: Simon W Hayward
• 金额: $ 31.2万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-29 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8566167
• 关键词: Address; Aging; Benign; Benign Prostatic Hypertrophy; Biological Assay; Biological Markers; Biological Models; Blood; Body Weight decreased; Caloric Restriction; Carbohydrates; Cells; Characteristics; Chronic; Clinical; Clinical Research; Complex; Data; Development; Diabetes Mellitus; Diet; Diet Habits; Dietary Component; Dinoprostone; Disease; Eating; Ensure; Epidemic; Epidemiologic Studies; Epidemiology; Epithelium; F2-Isoprostanes; Fatty acid glycerol esters; Genetic; Genitourinary system; Goals; Growth; Healthcare; Human; Hyperlipidemia; Hyperplasia; Immune; Inflammation; Inflammatory; Inflammatory Response; Insulin; Insulin Resistance; Knock-out; Link; Low Density Lipoprotein Receptor; Maintenance; Measures; Medicine; Metabolic; Metabolic stress; Methods; Modeling; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Operative Surgical Procedures; Oxidative Stress; Pathogenesis; Patients; Play; Process; Prostate; Prostatic; Prostatic Diseases; Prostatic hypertrophy; Regimen; Research; Resolution; Resources; Role; Serum; Severities; Stress; Sucrose; Symptoms; Techniques; Testing; Time; Tissues; United States; Urine; Weight; Work; adiponectin; bariatric surgery; design; dietary starch; feeding; human disease; in vivo Model; inflammatory marker; lower urinary tract symptoms; male health; men; model development; mouse model; multidisciplinary; prospective; prostaglandin M; receptor; response

Our overall approach is brings together a multidisciplinary team to determine the role of obesity in the development of benign prostatic hyperplasia (BPH). The research team has expertise in biological modeling of urogenital tract disease, epidemiology, and medicine, with special emphasis on model development and clinical manifestations of obesity, infiammation, and metabolic stress. The overall hypothesis is that benign hyperplastic growth of the prostate and associated infiammatory responses are influenced by obesity and diet. We further hypothesize that some of these changes may be reversed by appropriate dietary or surgical intervenfions, while others may become fixed. The project is broken into three aims, all centered on the links between BPH, infiammafion, and obesity. The first aim will test prostafic histopathologic changes, immune/inflammatory cell recruitment and systemic inflammatory marker changes induced in wild type, lepfin receptor knockout (ob/ob) and low density lipoprotein receptor knockout (LDLR-/-) C57/BL6 mice by high fat/high sucrose or high fat/high corn starch dietary regimens. Our preliminary data demonstrate that these models undergo prostatic changes consistent with aspects of human BPH. The second aim will examine the reversibility of these phenotypic and infiammatory changes using caloric restriction and Roux-en-Y gastric bypass (RYGB) surgery. These techniques will be applied to the mouse models at specific fimes in the development of inflammation and hyperplasia to determine which aspects of the disease process can be reversed by altering dietary habits. The third aim will take advantage of a NIDDK supported, prospective epidemiologic study of men with BPH (the Nashville Men's Health Study) to determine if blood and urine biomarkers of obesity and infiammafion and insulin expression and sensifivity are associated with levels of prostate tissue inflammation or BPH symptom progression over time. Speciflc Aims one and two are designed to determine the role of obesity in the induction and maintenance of specific markers of prostatic hyperplasia. Aim three extends these concepts to obesity, prostate tissue infiammation, and BPH progression in humans. The integrafion of these aims across mouse models and human epidemiology with overlapping biomarker panels will ground the mouse models to the clinical realifies of human BPH, while also developing an understanding of the mechanisms underiying disease pathogenesis.

我们的总体方法是汇集了一个多学科团队，以确定肥胖在 良性前列腺增生（BPH）的发展。研究团队在生物建模方面具有专业知识 泌尿生殖道疾病，流行病学和医学，特别着重于模型开发和 肥胖，感染和代谢压力的临床表现。 总体假设是前列腺的良性增生生长和相关的感染 反应受肥胖和饮食的影响。我们进一步假设其中一些变化可能是 通过适当的饮食或外科手术进行逆转，而其他人可能会固定。该项目是 分为三个目标，都集中在BPH，Infiammafion和肥胖之间的联系上。第一个目标 测试前列前的组织病理学变化，免疫/炎症细胞募集和全身性炎症 野生型，Lepfin受体敲除（OB/OB）和低密度脂蛋白受体引起的标记变化 敲除（LDLR - / - ）C57/BL6小鼠通过高脂肪/高蔗糖或高脂肪/高玉米淀粉饮食方案。我们的 初步数据表明，这些模型经历了前列腺变化，与 人BPH。第二个目标将检查这些表型和侵害性变化的可逆性 使用热量限制和roux-en-y胃旁路（RYGB）手术。这些技术将应用于 在发育和增生的发展中，在特定fime的小鼠模型确定哪个 疾病过程的各个方面可以通过改变饮食习惯来逆转。第三个目标将利用 BPH男性的NIDDK支持的前瞻性流行病学研究（纳什维尔男子健康研究） 确定肥胖和侵害和胰岛素表达和敏感性的血液和尿液生物标志物是否是 随着时间的流逝，前列腺组织炎症或BPH症状进展有关。 speciflc 目的一和两个旨在确定肥胖在特定的诱导和维持中的作用 前列腺增生的标记。目标三将这些概念扩展到肥胖，前列腺组织的侵蚀， 和人类的BPH进展。这些目标在鼠标模型和人类中的整合 与重叠生物标志物面板的流行病学将小鼠模型扎根于临床实现 人类BPH，同时还对疾病发病机理下的机制有了了解。